Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial

Abstract

Background:Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor.Objective:To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA).Methods:An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function.Results:Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis.Conclusion:Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression.Trial registration number:NCT00175877

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

“…Two new TNF inhibitors, golimumab (a fully human anti-TNF␣ monoclonal antibody) and certolizumab pegol (a PEGylated FabЈ fragment of a humanized anti-TNF monoclonal antibody), have more recently been shown to be effective in the treatment of RA (83)(84)(85)(86)(87)(88). Thus, TNF␣ has clearly been proven to be a good target for RA treatment and has fulfilled the expectations raised during the preclinical studies performed in animal models.…”

Comparison of Certolizumab Pegol with Other Anticytokine Agents for Treatment of Rheumatoid Arthritis: A Multiple-treatment Bayesian Metaanalysis

“…Being free of the Fc portion of the antibody, CZP does not form immune complexes, does not activate complement, and does not induce antibody-dependent cytotoxicity 4 . Efficacy and safety of CZP have been demonstrated in the treatment of RA 5,6 . CZP, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease-modifying antirheumatic drugs (DMARD), including MTX, has been inadequate.…”

“…Nineteen studies were selected in accordance with the predefined criteria and entered into the multiple-treatment metaanalysis 5,6,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37 (Figure 1). …”

Generalization and Extrapolation of Treatment Effects From Clinical Studies in Rheumatoid Arthritis

“…The effect of glucocorticoid treatment at baseline might be an indicator of disease activity, or the treatment itself might be of additional value, like cotreatment with a DMARD (33,34,40,42,43).…”